Colistin is an anti-bacterial cationic cyclic polypeptide belonging to the polymixin group. It is produced as a secondary metabolite of Bacillus polymyxa var. colistinus. Treatment of colistin base with formaldehyde and sodium bisulphite produces colistin sulphomethate sodium. The product is a crystalline powder which is soluble in water.
Colistin sulphomethate sodium, more commonly referred to as colistimethate sodium is a combination of the negatively charged molecular ion colistin sulphomethate with positive sodium ions. It should be carefully distinguished from colistin sulphate. Both are described in the European Pharmacopoeia.
Colistin is of particular benefit in the treatment of serious infections caused by bacterial pathogens such as Pseudomonas aeruginosa, Escherichia coli and Klebsiella spp. An important property of colistin is that bacteria sensitive to the drug do not readily acquire resistance. Colistin as a pharmaceutical may be prepared in numerous different preparations, e.g., topical, bladder irrigation, oral such as tablets, or as intravenous or intra-muscular injections.
Colistimethate sodium is a white to slightly yellow hygroscopic powder. It is commercially supplied at a particle size of 100-200 μm mass median diameter. The powder is highly soluble in water, slightly soluble in ethanol (96%) and is used for parenteral administration by dissolving in water. As a powder, colistin sulphomethate sodium must be stored in air-tight containers, preferably protected from light. Colistin sulphomethate sodium is used to treat infections in patients suffering from cystic fibrosis, a genetic disease which affects many body systems, and which develops at a young age. The disease is marked by a malfunction of the glands in the lining of the bronchial tubes. Instead of producing their normal thin mucus, the bronchial glands produce thick, sticky mucus that stagnates in the bronchial tubes. Microbes are able to multiply readily, causing serious respiratory infections, ultimately leading to respiratory failure. It is known that colistimethate sodium is effective in treatment of infections caused by these microbes e.g., Pseudomonas aeruginosa. The usual form of administration is as a solution for inhalation after nebulisation. The nebulised solution is prepared by taking a vial in which there is a known dosage of colistimethate sodium powder, injecting water into the vial and then inhaling the solution into the lungs through a nebuliser. Colistimethate sodium is poorly absorbed into the bloodstream. Therefore, this method of administration is preferred since bacteria can be attacked in the mucus which lines the lungs during illness.
Although colistin sulphomethate sodium is a valuable pharmaceutical in the treatment of infections occurring during cystic fibrosis and other bacterial infections, there are a number of disadvantages in drug delivery that have impeded acceptance as a treatment regime for cystic fibrosis, particularly for infants. It has been determined that many of the problems arise from the preferred delivery method described above, i.e., as a nebulised liquid. The present invention described herein addresses and solves this long-felt need in the art.